It is known to produce 4-acetoxyacetanilide by preparing the sodium salt of N-acetyl-para-aminophenol (APAP) and reacting such sodium salt with acetic anhydride. The APAP used as the starting material for the foregoing reaction is in turn prepared by catalytic hydrogenation of nitrobenzene with concomitant rearrangement in the presence of a platinum catalyst and aqueous sulfuric acid to form para-aminophenol, and acetylation of the latter compound with acetic anhydride to form the N-acetyl-para-aminophenol. This process is believed to present certain problems however, such as recovery of dissolved platinum catalyst used in the nitrobenzene reduction step. Furthermore, the acetylation step may present problems, such as the difficulty of monoacetylating the hydroxy aromatic amine, oligomerization of the hydroxy aromatic amine and color body formation.
It is also known to prepare APAP by hydrogenating 4-nitro-chlorobenzene to a 4-chloroaniline which is then reacted with aqueous KOH to form para-aminophenol. This is then acetylated as described previously to form the N-acetyl-para-aminophenol. This process is relatively complex requiring a fair number of reaction and purification steps. Moreover, the acetylation step in this process is believed to give rise to the same problems as occurs in the acetylation step of the nitrobenzene process described previously.
The preparation of hydroxy aromatic ketones by the Fries rearrangment of aromatic esters is well-known in the art. Thus, Lewis, U.S. Pat. No. 2,833,825 shows the rearrangement of phenyl or other aromatic esters to acylphenols or other hydroxy aromatic ketones using anhydrous hydrogen fluoride as catalyst. The examples of this patent are limited to the rearrangement of esters of higher fatty acids with the yields ranging from 55 to 95%.
Simons et al, Journal of the American Chemical Society, 62, 485 and 486 (1940) show the use of hydrogen fluoride as a condensing agent for various rearrangements and at page 486 show the Fries rearrangement of phenyl acetate to obtain p-hydroxyacetophenone.
Dann and Mylius in a dissertation included as part of a series of Reports from the Institute for Applied Chemistry of the University of Erlangen, received for publication on Jan. 7, 1954 and published in Annalen der Chemie 587 Band, pages 1 to 15 (1954), show the rearrangement of phenyl acetate in hydrogen fluoride to 4-hydroxyacetophenone, with a maximum yield of 81% after 24 hours of reaction time, and report a yield of 92% stated to be obtained by K. Weichert as reported in Angewandte Chemie 56, 338 (1943). However, Dann and Mylius suggest that the difference in yields may be at least partly due to the previous ignoring by Weichert of the accompanying 2-hydroxyacetophenone.
Dann and Mylius also disclose the reaction of phenol and glacial acetic acid in the presence of hydrogen fluoride to produce 4-hydroxyacetophenone at a yield of 61.6%. This reaction may be conventionally characterized as a Friedel-Crafts acetylation of phenol with acetic acid as the acetylating agent.
Simons et al, Journal of the American Chemical Society, 61, 1795 and 1796 (1939) teach the acylation of aromatic compounds using hydrogen fluoride as a condensing agent and in Table 1 on page 1796 show the acetylation of phenol with acetic acid to produce p-hydroxyacetophenone in 40% yield.
Meussdoerffer et al, German Offenlegungsschrift 26 16 986 published Oct. 27, 1977 and assigned to Bayer AG, disclose the acylation of phenolic compounds such as phenol itself with an acyl halide such as acetyl chloride to form hydroxy aromatic ketones.
Auwers et al, Chemische Berichte 1925, 58, 36-51, at page 41 show the Beckmann rearrangement of a large number of oximes of aromatic ketones most of which are substituted acetophenones. However, the only attempted rearrangement of the oxime of a ring-unsubstituted hydroxy aromatic ketone was that of the oxime of o-hydroxyacetophenone, but no amine was formed, i.e. the attempted rearrangement was unsuccessful; see Auwers et al at page 41.
Ganboa et al, Synthetic Communications 13(11), 941-944 (1983) show the production of acetanilide from acetophenone by refluxing in a solution of hydroxylamine hydrochloride. There is however no suggestion of the synthesis of N-acyl acyloxy aromatic amines such as 4-acetoxyacetanilide.
Pearson et al, Journal of the American Chemical Society 75 5905-5908 (Dec. 5, 1953) disclose the formation of hydrazones from ketones by reaction with hydrazine hydrate and the rearrangement of the hydrazone to the amide by reaction with sodium nitrite and concentrated sulfuric acid. Specifically, on page 5907 Pearson et al show the rearrangement of p-hydroxyacetophenone hydrazone to p-hydroxyacetanilide, i.e. APAP.